[go: up one dir, main page]

EP2851361B1 - Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits, et procédé pour produire ceux-ci - Google Patents

Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits, et procédé pour produire ceux-ci Download PDF

Info

Publication number
EP2851361B1
EP2851361B1 EP13790465.2A EP13790465A EP2851361B1 EP 2851361 B1 EP2851361 B1 EP 2851361B1 EP 13790465 A EP13790465 A EP 13790465A EP 2851361 B1 EP2851361 B1 EP 2851361B1
Authority
EP
European Patent Office
Prior art keywords
unsaturated fatty
highly unsaturated
fatty acid
fatty acids
ethyl ester
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP13790465.2A
Other languages
German (de)
English (en)
Other versions
EP2851361A1 (fr
EP2851361A4 (fr
Inventor
Nobushige Doisaki
Kazuhiko Hata
Shinji TOKIWA
Kazunori MATSUSHIMA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nissui Corp
Original Assignee
Nippon Suisan Kaisha Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=49583751&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP2851361(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Nippon Suisan Kaisha Ltd filed Critical Nippon Suisan Kaisha Ltd
Priority to EP24178220.0A priority Critical patent/EP4414356A3/fr
Priority to EP21206640.1A priority patent/EP3971165B1/fr
Publication of EP2851361A1 publication Critical patent/EP2851361A1/fr
Publication of EP2851361A4 publication Critical patent/EP2851361A4/fr
Application granted granted Critical
Publication of EP2851361B1 publication Critical patent/EP2851361B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
    • C07C51/44—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation by distillation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
    • C07C69/587—Monocarboxylic acid esters having at least two carbon-to-carbon double bonds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D3/00—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping
    • B01D3/14—Fractional distillation or use of a fractionation or rectification column
    • B01D3/143—Fractional distillation or use of a fractionation or rectification column by two or more of a fractionation, separation or rectification step
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/47—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C07C57/03—Monocarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C07C57/03—Monocarboxylic acids
    • C07C57/12—Straight chain carboxylic acids containing eighteen carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/48—Separation; Purification; Stabilisation; Use of additives
    • C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
    • C07C67/54—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/48—Separation; Purification; Stabilisation; Use of additives
    • C07C67/56—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B3/00—Refining fats or fatty oils
    • C11B3/12—Refining fats or fatty oils by distillation
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
    • C11C1/00—Preparation of fatty acids from fats, fatty oils, or waxes; Refining the fatty acids
    • C11C1/02—Preparation of fatty acids from fats, fatty oils, or waxes; Refining the fatty acids from fats or fatty oils
    • C11C1/04—Preparation of fatty acids from fats, fatty oils, or waxes; Refining the fatty acids from fats or fatty oils by hydrolysis
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
    • C11C3/00—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom
    • C11C3/003—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom by esterification of fatty acids with alcohols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS OR COOKING OILS
    • A23D9/00—Other edible oils or fats, e.g. shortenings or cooking oils
    • A23D9/02—Other edible oils or fats, e.g. shortenings or cooking oils characterised by the production or working-up
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/60—Fish, e.g. seahorses; Fish eggs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/612—Crustaceans, e.g. crabs, lobsters, shrimps, krill or crayfish; Barnacles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
    • B01D15/32—Bonded phase chromatography
    • B01D15/325—Reversed phase
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B3/00—Refining fats or fatty oils
    • C11B3/16—Refining fats or fatty oils by mechanical means

Definitions

  • the present invention relates to a method for reducing the quantities of environmental pollutants, in particular, dioxins, brominated flame retardants, and other substances contained in fats or oils containing the highly unsaturated fatty acids in the production of highly unsaturated fatty acids or highly unsaturated fatty acid ethyl esters from the fats or oils.
  • the present invention further relates to foods, supplements, medicines, cosmetics and feeds that are produced from the fats or oils prepared in accordance with such methods.
  • Environmental pollutants typified by dioxins are found almost everywhere on Earth today. They are also known to exert effects on fishes living in polluted ocean areas. They are considered to have no direct effects on health if present in trace amounts but, nevertheless, the ingredients to be ingested by humans as foods or feeds desirably contain the least amounts of environmental pollutants.
  • Marine product oils for example, fish oils contain highly unsaturated fatty acids such as EPA (eicosapentaenoic acid, C20:5, n-3, all-cis-5,8,11,14,17-eicosdapentaenoic acid) and DHA (docosahexaenoic acid, C22:6, n-3, all-cis-4,7,10,13,16,19-docosahexaenoic acid).
  • EPA and DHA are used as ingredients of medicines, health foods, foods in general, feeds and the like.
  • Various purification steps are applied to make use of the EPA and/or DHA in marine product oils.
  • Non-Patent Document 1 discloses removing the insecticide DDT and its metabolites from fish oils by molecular distillation.
  • Non-Patent Document 2 discloses that chlorinated hydrocarbons and free fatty acids can be removed from fats or oils using vacuum stripping or thin-film distillation.
  • Non-Patent Document 3 discloses using physical refining and molecular distillation in order to remove free fatty acids and other undesired substances from oil compositions.
  • Patent Document 1 and Non-Patent Document 4 each disclose a method for reducing the quantities of environmental pollutants in a mixture containing fats or oils which comprises the step of adding a volatile working fluid to the mixture and the step of subjecting the mixture to at least one stripping process together with the added volatile working fluid.
  • Non-Patent Document 5 discloses that highly unsaturated fatty acids are decomposed thermally when fish oils are deodorized at high temperatures.
  • Non-Patent Document 6 discloses removing dioxins, free fatty acids and cholesterols from fish oils by short path distillation so as to make them suitable for use as feedstocks for ethyl esters.
  • Patent Document 2 discloses a method for producing a concentrate of eicosapentaenoic and docosahexaenoic acid esters with low content of persistent organic pollutants.
  • An object of the present invention is to provide a method for reducing the quantities of environmental pollutants, in particular, dioxins and brominated flame retardants, contained in fats or oils that contain the highly unsaturated fatty acids as constituent fatty acids in the production of ethyl esters of highly unsaturated fatty acids from the fats or oils; another object of the present invention is to provide ethyl esters having smaller contents of the dioxins and brominated flame retardants.
  • the invention is defined by the claims. Any subject-matter falling outside the scope of the claims is provided for information purposes only.
  • the present invention has been completed on the basis of the finding that if fats or oils in which those highly unsaturated fatty acids that are prone to deteriorate as through oxidation or isomerization are contained as constituent fatty acids are refined by performing molecular distillation or short path distillation under specified conditions, the concentrations of environmental pollutants can be reduced to very low levels while suppressing the deterioration of the highly unsaturated fatty acids.
  • the quantities of environmental pollutants in the fats or oils can be reduced in such a way that the total content of dioxins is less than 0.2 pg-TEQ/g where TEQ is short for toxicity equivalency quantity.
  • ethyl esters can be obtained using the thus processed fats or oils as a feedstock.
  • the quantities of dioxins in the ethyl esters can be further reduced.
  • the present invention relates to the highly unsaturated fatty acids or highly unsaturated fatty acid ethyl esters described below and the methods of producing the same, as well as feeds, foods, medicines, etc. that contain the same.
  • the method of the present invention ensures that by virtue of distillation at high temperatures in high vacuum over a short period of time, the quantities of environmental pollutants, and dioxins in particular, that are contained in fish oils and the like can be reduced to very low levels without affecting the percentage of highly unsaturated fatty acids in the sum of fatty acids and, hence, it is possible to provide feeds, foods, supplements, medicines and various other products as prepared from fish oils and other feedstocks with which there is no need to worry about contamination by dioxins.
  • highly unsaturated fatty acids refers to fatty acids containing at least 18 carbon atoms and at least 3 double bonds, more preferably fatty acids containing at least 20 carbon atoms and at least 3 or 4 double bonds, and most preferably fatty acids containing at least 20 carbon atoms and at least 5 double bonds.
  • ⁇ -linoleic acid (18:3, n-3), ⁇ -linoleic acid (18:3, n-6), dihomo- ⁇ -linoleic acid (20:3, n-6), arachidonic acid (20:4, n-6), eicosapentaenoic acid (20:5, n-3), docosapentaenoic acid (22:5, n-6), docosahexaenoic acid (22:6, n-3), etc.
  • microorganism oils such as sardine oil, tuna oil, bonito oil, Men Hayden oil, cod liver oil, herring oil, capelin oil, and salmon oil
  • marine animal oils as from crustaceans such as krill
  • vegetable oils as from perilla, flax, soybean, and rapeseed
  • the method of the present invention is suitable for application to fats or oils derived from marine products with which there are particular concerns about contamination by dioxins, as exemplified by fish oils, krill oil, or marine mammal oils.
  • fats or oils containing highly unsaturated fatty acids as constituent fatty acids means triglycerides or phospholipids.
  • preliminary treatments may be performed before they are subjected to molecular distillation or short path distillation.
  • the preliminary treatments may be exemplified by a degumming step, a decoloring step using activated clay or activated charcoal, and a washing step with water.
  • the term "environmental pollutants” embraces: polychlorinated biphenyls (PCBs), DDTs, polychlorinated triphenyls (PCTs), dibenzo-dioxins (PCDDs), and dibenzo-furans (PCDFs); chlorophenols and hexachlorocyclohexanes (HCHs), toxaphenes, dioxins, brominated flame retardants, polyaromatic hydrocarbons (PAHs), organotin compounds (e.g. tributyltin and triphenyltin), organomercury compounds (e.g. methylmercury), etc.
  • PCBs polychlorinated biphenyls
  • PCTs polychlorinated triphenyls
  • PCDDs dibenzo-dioxins
  • PCDFs dibenzo-furans
  • dioxins refers to the sum of the polychlorinated dibenzoparadioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar PCBs (Co-PCBs) that are listed in Table 1 below; the contents of the respective members were measured, each measured value was multiplied by the corresponding toxicity equivalency factor and summed up to calculate the toxicity equivalency quantity (pg-TEQ/g).
  • PCDDs polychlorinated dibenzoparadioxins
  • PCDFs polychlorinated dibenzofurans
  • Co-PCBs coplanar PCBs
  • brominated flame retardants collectively refers to the compounds listed in Table 9 below. Although contamination by dioxins in the environment has recently begun to decrease, contamination by brominated flame retardants still tends to increase and hence deserves special note. Applicable indicators are BDE-100, BDE-49, BDE-99, and BDE-47 which are relatively high amount in fish oils.
  • dioxins are removed by thin-film distillation, preferably by molecular distillation or short path distillation (SPD).
  • SPD short path distillation
  • one that is performed with the condenser placed within a shorter distance than the mean free path of the vapor molecules evaporating from the heating surface at a specified pressure under a high vacuum ( ⁇ 0.1 Pa) is called molecular distillation.
  • Short path distillation has been developed with a view to enhancing the distilling performance of molecular distillation.
  • Short path distillation is performed at pressures in a medium vacuum region higher than 0.1 Pa, with the condenser placed at distances approximately equal to the mean free path of the evaporating molecules, so it is a practical method that is by far improved in distilling performance than molecular distillation.
  • molecular distillation or short path distillation is carried out at a temperature of 200-270°C, preferably 220-260°C, and more preferably 220-250°C. Both types of distillation are carried out at a pressure lower than 5 Pa, preferably lower than 2 Pa, and more preferably lower than 1 Pa. They are performed by the thin-film method that is carried out at a flow rate of 20-200 (kg/h)/m 2 , preferably 25-120 (kg/h)/m 2 . If the flow volume is unduly small, the productivity will drop, so it is preferred to flow the feedstock oil in a maximum removable volume while ensuring that dioxins are being removed. If distillation is performed under these conditions, highly unsaturated fatty acids, although being heat-sensitive, will suffer little deterioration in quality.
  • the quantities of dioxins PCDDs and PCDFs could be reduced to below the limit of measurement, or substantially zero.
  • the value zero typically means less than 0.043 pg-TEQ/g as calculated from the numerical values of detection limit listed in Table 6; in other words, the quantities of dioxins PCDDs and PCDFs can be reduced to less than 0.05 pg-TEQ/g.
  • the quantities of coplanar PCBs can also be reduced to less than 0.2 pg-TEQ/g, even to less than 0. 1 pg-TEQ/g, or to less than 0.05 pg-TEQ/g, or to less than 0.02 pg-TEQ/g, and even to less than 0.01 pg-TEQ/g.
  • brominated flame retardants if BDE-100, BDE-49, BDE-99 and BDE-47 are chosen as indicators, their quantities can be reduced to less than 0.05 ⁇ g/g, preferably less than 0.03 ⁇ g/g, and more preferably less than 0.02 ⁇ g/g.
  • the feedstock oil is preferably one that has been subjected to a degumming process as by washing with water.
  • the washed feedstock oil is immediately subjected to molecular distillation or short path distillation under the conditions described above, so that cholcsterols, free fatty acids, environmental pollutants and the like are removed as distillate fractions, yielding the residue containing triglycerides.
  • the residue may be used either immediately or after being subjected to a decoloring process as with activated charcoal or activated clay or to a deodorizing process as by steam distillation.
  • the refined fat or oil thus produced can be used as an ingredient in feeds, foods, or supplements.
  • the above-mentioned residue may be used as a feedstock for producing ethyl esters containing dioxins in reduced amounts.
  • ethyl alcohol and a catalyst or an enzyme are added to the residue and reaction is performed to generate esters of the constituent fatty acids of the triglyceride and the ethyl alcohol.
  • This step of ethyl esterification may be performed by any known method.
  • the formed ethyl ester may be further refined.
  • an additional method such as molecular distillation, rectification or column chromatography may be applied.
  • refining can be achieved by such methods as disclosed in JP H5-222392 (Family Patent EP0610506 ), JP H4-41457 (Family Patent EP0460917 ), JP H6-33088 , etc.
  • Rectification is performed under a high vacuum with three or more distillation columns and the main distillate consisting of the EPA ethyl ester and/or DHA ethyl ester is separated from an initial fraction of the higher volatility and a bottoms fraction of the lower volatility.
  • the conditions of rectification are such that the temperature is in the range of 150-200°C, preferably 160-190°C, more preferably 170-190°C and the pressure is in the range of 1-300 Pa, preferably 1-200 Pa, more preferably 1-133 Pa. It is preferred that the main distillate of 160-190°C, preferably 170-190°C is obtained with the degree of vacuum being chosen at 1-133 Pa.
  • a particularly preferred method is by performing column chromatography after rectification.
  • the present inventors found that as the result of concentrating EPA and DHA by rectification, the relative concentrations of dioxins rose but that by means of subsequent column chromatography, they could be rendered lower than the levels prior to the rectification.
  • silica gel, ion-exchange resin, activated clay, silver nitrate, etc. may be used in column chromatography, it is particularly preferred to perform column chromatography of reverse-phase distribution type.
  • a reverse-phase distribution system may be created by using, for example, an alkyl group bound silica packing material (e.g. ODS column), with water, alcohols or ketones being used as solvent. Methanol is preferred. These solvents may be used either independently or in admixture.
  • highly unsaturated fatty acids can be concentrated while reducing the concentrations of environmental pollutants.
  • concentrations of highly unsaturated fatty acids say, EPA ethyl ester and/or DHA ethyl ester, can be increased to a purity of at least 80area%, or at least 85area%, or at least 90area%, or 95area%, or even at least 96area% while, at the same time, among the dioxins, PCDDs and PCDFs can be reduced in content below their limits of measurement, namely, substantially zero (less than 0.043 pg-TEQ/g as calculated from the detection limits) and the contents of coplanar PCBs can also be lowered to less than 0.1 pg-TEQ/g, or less than 0.03 pg-TEQ/g, or even less than 0.01 pg-TEQ/g.
  • the brominated flame retardants their quantities can be lowered to less than 0.18 ng/g in terms of BDE-47, to less than 0.03 ng/g in terms of BDE-100, to less than 0.05 ng/g in terms of BDE-49, and to less than 0.05 ng/g in terms of BDE-99.
  • the quantities of BDE-100, BDE-49, BDE-99 and BDE-47 can be lowered to less than 0.05 ⁇ g/g, preferably less than 0.03 ⁇ g/g, more preferably less than 0.02 ⁇ g/g.
  • the concentration of EPA ethyl ester and/or DHA ethyl ester is preferably equivalent to a purity of at least 96area%.
  • the EPA and/or DHA in fatty acids need be concentrated to a higher content depending on the need.
  • the highly unsaturated fatty acids in the glyceride may be concentrated by a method for selective concentration of highly unsaturated fatty acids through lipase reaction (as disclosed in WO2009/17102 ). Even the thus processed glyceride may be treated by the method of the present invention to have higher concentrations of highly unsaturated fatty acids but lower quantities of environmental pollutants.
  • the highly unsaturated fatty acid esters produced by the method described above may be hydrolyzed to give the highly unsaturated fatty acids.
  • a measurement of brominated flame retardants was commissioned to "eurofins", a bio-analytical testing company.
  • the method of the measurement was in accordance with high-resolution mass spectrometry (HRGC/HRMS).
  • composition of fatty acids in a feedstock fish oil and that of fatty acids in the oil resulting from subsequent short path distillation were determined by gas chromatography after ethyl esterification of the fish oil.
  • 1 mL of 1 N sodium ethylate/ethanol solution was added to 40 ⁇ L of fish oil and the resulting mixture was stirred for about 30 seconds.
  • 1 mL of 1 N hydrochloric acid was added to neutralize the mixture, to which 2 mL of hexane and 3 mL of a saturated aqueous solution of ammonia sulfate were added; after allowing the stirred mixture to settle undisturbed, the upper layer was subjected to measurement by gas chromatography.
  • the distillation apparatus used was a short path distillation (SPD) device KD 10 (product of UIC GmbH with a distillation surface area of 0.1 m 2 ).
  • the distillation conditions (temperature, pressure, and flow rate) were as shown in Table 2. With the distillation temperature fixed at 250°C, the pressure and flow rate were varied within the ranges of 0.4-3.0 Pa and 25-121 (kg/hr)/m 2 , respectively.
  • dioxins were removed from semi refined tuna oil (refined by degumming and deacidification) by distillation under the conditions listed in Table 3.
  • Table 3 shows, the contents of dioxins in the tuna oil could also be reduced to less than 0.1 pg-TEQ/g by the method of the present invention (distilled at a temperature of 250°C, at a pressure of 0.1 Pa, and at a flow rate of 48 (kg/hr)/m 2 ).
  • dioxins were removed from crude sardine oil.
  • SPD short path distillation
  • Table 3 shows, the contents of dioxins could also be reduced to less than 0.1 pg-TEQ/g by the method of the present invention (distilled at a temperature of 270°C, at a pressure of 0.6 Pa, and at a flow rate of 20 (kg/hr)/m 2 ).
  • a crude sardine oil (with an acid value of 6 and containing 19% EPA and 8% DHA) was washed with warm (85°C) water (5% relative to the crude oil) and subjected to short path distillation using a short path distillation (SPD) device KD1800 (product of UIC GmbH, with a distillation surface area of 18 m 2 ).
  • the distillation conditions were as follows: degree of vacuum, 0.7-1 Pa; device temperature, 250°C; feed volume, ca. 2000 kg/H (flow rate: 110 (kg/h)/ m 2 ).
  • the results of measurement of dioxins in oil are shown in Table 5 (for the feedstock oil) and Table 6 (for the SPD oil).
  • the total quantity of dioxins could be reduced from 3.0 pg-TEQ/g to 0.014 pg-TEQ/g in terms of toxicity equivalency quantity.
  • the acid value of the SPD oil was less than 0.2 and there was no change in the composition of fatty acids from the crude oil.
  • ARA arachidonic acid and DPA docosapentaenoic acid.
  • the production procedure was as follows: the SPD oil was subjected to ethanolysis reaction with ethyl alcohol in the presence of an alkali catalyst to form an ethyl ester: after washing with warm water, the ethyl ester was dried and rectified with a degree of vacuum of 13 Pa to give the main distillate (with a temperature of ca. 176°C), which was treated by HPLC using column of reverse-phase distribution type (ODS); the solvent was subsequently distilled off to yield an ethyl ester of 97% pure EPA.
  • ODS reverse-phase distribution type
  • the rectification and column chromatographic processing in the refining step after ethyl esterification were verified for possible effects they might have on the concentration of dioxins.
  • the feedstock oil was sardine oil that was simply diacidified and decolored without subsequent thin-film distillation. This was because use of fats or oils containing more dioxins would provide greater ease in observing the possible effects of the refining process.
  • the feedstock oil was ethyl esterified using an alkali catalyst.
  • the resulting ethyl esters were first subjected to a rectification step, thereby collecting fractions containing ethyl esters of C 20 fatty acids. Subsequently, a fraction of eicosapentaenoic acid ethyl ester was collected by ODS column chromatography.
  • Table 9 shows data for the four components that experienced greater variations (in terms of absolute value and toxicity equivalency quantity) and the total of dioxins (in toxicity equivalency quantity).
  • the rectification step caused the components #105 and #118 to be concentrated by far greater degrees than when they were just after the esterification. On the other hand, the content of #77 decreased rather than increased. It is assumed that in rectification, ethyl esters of eicosapentaenoic acid and other fatty acids behaved in a similar way to dioxins, so that the dioxins were concentrated as were the ethyl esters of eicosapentaenoic acid and other fatty acids.
  • the amounts of environmental contaminants, especially dioxins and brominated flame retardants, that are contained in fats or oils that comprise highly unsaturated fatty acids as constituent fatty acid, as exemplified by fish oils containing EPA and DHA can be markedly reduced, making it possible to provide fats or oils having this feature.
  • the products thus obtained are suitable for use in feeds, foods, supplements, medicines, and the like.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Nutrition Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • Emergency Medicine (AREA)
  • Mycology (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Analytical Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Fats And Perfumes (AREA)
  • Edible Oils And Fats (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Developmental Biology & Embryology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Marine Sciences & Fisheries (AREA)

Claims (20)

  1. Acide(s) gras hautement insaturé(s) ou ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) qui a / ont été produit(s) en utilisant, comme huile de base, une graisse ou une huile dérivée d'un produit marin qui contient des acides gras hautement insaturés, en tant qu'acides gras constitutifs, et qui a été réduit dans les teneurs en polluants environnementaux ;
    où, parmi les dioxines contenues, des dibenzoparadioxines polychlorées (PCDD) et des dibenzofuranes polychlorés (PCDF) sont contenus suivant des quantités de moins de 0,05 pg-TEQ/g, et des biphényles polychlorés coplanaires (Co-PCB) sont contenus suivant des quantités de moins de 0,03 pg-TEQ/g ;
    où lesdites quantités d'équivalence de toxicité - TEQ - sont calculées en se basant sur les facteurs d'équivalence de toxicité (TEF) selon l'OMS (2006) ;
    où le ou les acide(s) gras hautement insaturé(s) est / sont un ou des acide(s) gras contenant au moins 18 atomes de carbone et au moins 3 doubles liaisons ;
    où la concentration de l'acide ou des acides gras hautement insaturé(s), dans le total d'acides gras, est au moins de 80 % en surface, telle que ladite concentration a été déterminée par chromatographie en phase gazeuse ;
    où les dibenzoparadioxines polychlorées (PCDD) sont sélectionnées parmi le groupe se composant de 2,3,7,8-tétrachlorodibenzo-p-dioxine, de 1,2,3,7,8-pentachlorodibenzo-p-dioxine, de 1,2,3,4,7,8-hexachlorodibenzo-p-dioxine, de 1,2,3,6,7,8-hexachlorodibenzo-p-dioxine, de 1,2,3,7,8,9-hexachlorodibenzo-p-dioxine, de 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxine et d'octachlorodibenzo-p-dioxine ;
    où les dibenzofuranes polychlorés (PCDF) sont sélectionnés parmi le groupe se composant de 2,3,7,8-tétrachlorodibenzofurane, de 1,2,3,7,8-pentachlorodibenzofurane, de 2,3,4,7,8-pentachlorodibenzofurane, de 1,2,3,4,7,8-hexachlorodibenzofurane, de 1,2,3,6,7,8-hexachlorodibenzofurane, de 1,2,3,7,8,9-hexachlorodibenzofurane, de 2,3,4,6,7,8-hexachlorodibenzofurane, de 1,2,3,4,6,7,8-heptachlorodibenzofurane, de 1,2,3,4,7,8,9-heptachlorodibenzofurane et d'octachlorodibenzofurane ; et
    où les biphényles polychlorés coplanaires (Co-PCB) sont sélectionnés parmi le groupe se composant de 3,4,4',5-tétrachlorobiphényle, de 3,3',4,4'-tétrachlorobiphényle, de 3,3',4,4',5-pentachlorobiphényle, de 3,3',4,4',5,5'-hexachlorobiphényle, de 2',3,4,4',5-pentachlorobiphényle, de 2,3',4,4',5-pentachlorobiphényle, de 2,3,3',4,4'-pentachlorobiphényle, de 2,3,4,4',5-pentachlorobiphényle, de 2,3',4,4',5,5'-hexachlorobiphényle, de 2,3,3',4,4',5-hexachlorobiphényle, de 2,3,3',4,4',5'-hexachlorobiphényle, de 2,3,3',4,4',5,5'-heptachlorobiphényle.
  2. Acide(s) gras hautement insaturé(s) ou ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) selon la revendication 1, où la teneur en retardateur de flamme bromé, qui est contenu, a été réduite à un niveau tel que la quantité de BDE-47 est inférieure à 0,18 ng/g, la quantité de BDE-100 est inférieure à 0,03 ng/g, la quantité de BDE-49 est inférieure à 0,05 ng/g ou la quantité de BDE-99 est inférieure à 0,05 ng/g.
  3. Ester(s) éthylique(s) d'acide(s) gras hautement insaturé (s) selon la revendication 1 ou 2, où la concentration d'un ou des acide (s) gras hautement insaturé(s), dans le total d'acide(s) gras, est au moins de 85 % en surface, au moins de 90 % en surface, au moins de 95 % en surface ou au moins de 96 % en surface.
  4. Acide(s) gras hautement insaturé(s) ou ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) selon l'une quelconque des revendications 1 à 3, où la graisse ou l'huile contenant des acides gras hautement insaturés, en tant qu'acides gras constitutifs, est de l'huile de poisson, de l'huile de krill ou de l'huile d'un mammifère marin.
  5. Acide(s) gras hautement insaturé(s) ou ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) selon l'une quelconque des revendications 1 à 4, où le ou les acide(s) gras hautement insaturé(s) est / sont l'un quelconque d'un acide eicosapentaénoïque, d'un acide docosahexaénoïque, d'un acide docosapentaénoïque, d'un acide dihomo-γ-linolénique et d'un acide arachidonique ou une combinaison de ces acides.
  6. Médicament, supplément ou aliment qui comprend le ou les acide(s) gras hautement insaturé(s) ou le ou les ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) selon l'une quelconque des revendications 1 à 5.
  7. Procédé de production d'un ou d'acide(s) gras hautement insaturé(s) ou d'un ou d'ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) avec des teneurs réduites en dibenzoparadioxines polychlorées (PCDD), en dibenzofuranes polychlorés (PCDF) et en PCB coplanaires (Co-PCB), ledit procédé étant mis en œuvre par les étapes :
    a) d'élimination d'acides gras libres et de polluants environnementaux par une distillation en couche mince, à partir d'une huile de base contenant des acides gras hautement insaturés en tant qu'acides gras constitutifs ;
    b) d'hydrolyse ou d'estérification éthylique de l'acide gras hautement insaturé ayant été obtenu, ledit acide gras contenant de la graisse ou de l'huile ; et
    c) d'affinage de ce même acide gras par rectification et par chromatographie sur colonne ;
    où des acides gras hautement insaturés sont des acides gras contenant au moins 18 atomes de carbone et au moins 3 doubles liaisons,
    où la concentration d'acides gras hautement insaturés, dans le total d'acides gras dans le ou les acide(s) gras hautement insaturé(s) ou dans le ou les ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s), est au moins de 80 % en surface, telle que ladite concentration a été déterminée par chromatographie en phase gazeuse.
  8. Procédé selon la revendication 7, dans lequel la teneur en retardateur de flamme bromé est également réduite.
  9. Procédé selon la revendication 7 ou 8, dans lequel la concentration d'acides gras hautement insaturés dans le total d'acides gras dans le ou les acide(s) gras hautement insaturé(s) ou dans le ou les ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) est au moins de 85 % en surface, au moins de 90 % en surface, au moins de 95 % en surface ou au moins de 96 % en surface.
  10. Procédé selon l'une quelconque des revendications 7 à 9, dans lequel l'huile de base contenant des acides gras hautement insaturés, en tant qu'acides gras constitutifs, est de l'huile de poisson, de l'huile de krill, de l'huile d'un mammifère marin ou de l'huile d'un microorganisme.
  11. Procédé selon l'une quelconque des revendications 7 à 10, dans lequel la distillation en couche mince est effectuée à une température de 200°C-270°C, de 220°C-260°C ou de 220°C-250°C.
  12. Procédé selon l'une quelconque des revendications 7 à 11, dans lequel la distillation en couche mince est effectuée à une pression de 5 Pa ou moins, de 2 Pa ou moins ou de 1 Pa ou moins.
  13. Procédé selon l'une quelconque des revendications 7 à 12, dans lequel la distillation en couche mince est effectuée à un débit de 20-200 (kg/h)/m2 ou de 25-120 (kg/h)/m2.
  14. Procédé selon l'une quelconque des revendications 7 à 13, dans lequel la distillation en couche mince est une distillation moléculaire ou une distillation à trajet court.
  15. Procédé selon l'une quelconque des revendications 7 à 14, dans lequel la rectification est effectuée dans trois colonnes de distillation ou plus.
  16. Procédé selon l'une quelconque des revendications 7 à 15, dans lequel l'affinage par chromatographie sur colonne utilise une chromatographie sur colonne du type de distribution par inversion de phase.
  17. Acide(s) gras hautement insaturé(s) ou ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) qui a / ont été produit (s) par le procédé selon l'une quelconque des revendications 7 à 16 et dont la teneur en dioxines est inférieure à 0,07 pg-TEQ/g ou à 0,05 pg-TEQ/g,
    où ladite quantité d'équivalence de toxicité - TEQ - est calculée en se basant sur les facteurs d'équivalence de toxicité (TEF) selon l'OMS (2006),
    où des acides gras hautement insaturés sont des acides gras contenant au moins 18 atomes de carbone et au moins 3 doubles liaisons,
    où des dioxines sont le total des dibenzoparadioxines polychlorées (PCDD), des dibenzofuranes polychlorés (PCDF) et des biphényles polychlorés coplanaires (Co-PCB),
    où les dibenzoparadioxines polychlorées (PCDD) sont sélectionnées parmi le groupe se composant de 2,3,7,8-tétrachlorodibenzo-p-dioxine, de 1,2,3,7,8-pentachlorodibenzo-p-dioxine, de 1,2,3,4,7,8-hexachlorodibenzo-p-dioxine, de 1,2,3,6,7,8-hexachlorodibenzo-p-dioxine, de 1,2,3,7,8,9-hexachlorodibenzo-p-dioxine, de 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxine et d'octachlorodibenzo-p-dioxine,
    où les dibenzofuranes polychlorés (PCDF) sont sélectionnés parmi le groupe se composant de 2,3,7,8-tétrachlorodibenzofurane, de 1,2,3,7,8-pentachlorodibenzofurane, de 2,3,4,7,8-pentachlorodibenzofurane, de 1,2,3,4,7,8-hexachlorodibenzofurane, de 1,2,3,6,7,8-hexachlorodibenzofurane, de 1,2,3,7,8,9-hexachlorodibenzofurane, de 2,3,4,6,7,8-hexachlorodibenzofurane, de 1,2,3,4,6,7,8-heptachlorodibenzofurane, de 1,2,3,4,7,8,9-heptachlorodibenzofurane et d'octachlorodibenzofurane, et
    où les biphényles polychlorés coplanaires (Co-PCB) sont sélectionnés parmi le groupe se composant de 3,4,4',5-tétrachlorobiphényle, de 3,3',4,4'-tétrachlorobiphényle, de 3,3',4,4',5-pentachlorobiphényle, de 3,3',4,4',5,5'-hexachlorobiphényle, de 2',3,4,4',5-pentachlorobiphényle, de 2,3',4,4',5-pentachlorobiphényle, de 2,3,3',4,4'-pentachlorobiphényle, de 2,3,4,4',5-pentachlorobiphényle, de 2,3',4,4',5,5'-hexachlorobiphényle, de 2,3,3',4,4',5-hexachlorobiphényle, de 2,3,3',4,4',5'-hexachlorobiphényle, de 2,3,3',4,4',5,5'-heptachlorobiphényle.
  18. Acide(s) gras hautement insaturé(s) ou ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) selon la revendication 17, où la teneur en retardateur de flamme bromé, qui est contenu, a été réduite à un niveau tel que la quantité de BDE-47 est inférieure à 0,18 ng/g, la quantité de BDE-100 est inférieure à 0,03 ng/g, la quantité de BDE-49 est inférieure à 0,05 ng/g ou la quantité de BDE-99 est inférieure à 0,05 ng/g.
  19. Acide(s) gras hautement insaturé(s) ou ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) selon la revendication 17 ou 18, où la concentration d'acides gras hautement insaturés, dans le total d'acides gras, est au moins de 80 % en surface, au moins de 85 % en surface, au moins de 90 % en surface, au moins de 95 % en surface ou au moins de 96 % en surface, telle que ladite concentration a été déterminée par chromatographie en phase gazeuse.
  20. Médicament, supplément ou aliment qui contient le ou les acide(s) gras hautement insaturé(s) ou le ou les ester(s) éthylique(s) d'acide(s) gras hautement insaturé(s) selon l'une quelconque des revendications 17 à 19.
EP13790465.2A 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits, et procédé pour produire ceux-ci Active EP2851361B1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP24178220.0A EP4414356A3 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits et leur procédé de production
EP21206640.1A EP3971165B1 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits et leur procédé de production

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2012110809 2012-05-14
PCT/JP2013/063425 WO2013172346A1 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec polluants environnementaux réduits, et procédé pour produire ceux-ci

Related Child Applications (2)

Application Number Title Priority Date Filing Date
EP21206640.1A Division EP3971165B1 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits et leur procédé de production
EP24178220.0A Division EP4414356A3 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits et leur procédé de production

Publications (3)

Publication Number Publication Date
EP2851361A1 EP2851361A1 (fr) 2015-03-25
EP2851361A4 EP2851361A4 (fr) 2015-12-30
EP2851361B1 true EP2851361B1 (fr) 2021-11-24

Family

ID=49583751

Family Applications (3)

Application Number Title Priority Date Filing Date
EP24178220.0A Pending EP4414356A3 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits et leur procédé de production
EP13790465.2A Active EP2851361B1 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits, et procédé pour produire ceux-ci
EP21206640.1A Active EP3971165B1 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits et leur procédé de production

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP24178220.0A Pending EP4414356A3 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits et leur procédé de production

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP21206640.1A Active EP3971165B1 (fr) 2012-05-14 2013-05-14 Acide gras hautement insaturé ou ester éthylique d'acide gras hautement insaturé avec des polluants environnementaux réduits et leur procédé de production

Country Status (13)

Country Link
US (7) US9540306B2 (fr)
EP (3) EP4414356A3 (fr)
JP (8) JP5592570B2 (fr)
KR (8) KR102117806B1 (fr)
CN (5) CN113045422A (fr)
CA (2) CA2873160C (fr)
CL (1) CL2014003053A1 (fr)
DE (1) DE202013012875U1 (fr)
DK (1) DK2851361T3 (fr)
ES (2) ES2900618T3 (fr)
HU (1) HUE057283T2 (fr)
PE (3) PE20241184A1 (fr)
WO (1) WO2013172346A1 (fr)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102117806B1 (ko) * 2012-05-14 2020-06-01 닛폰 스이산 가부시키가이샤 환경 오염 물질을 저감시킨 고도 불포화 지방산 또는 고도 불포화 지방산 에틸에스테르 및 그 제조 방법
WO2014068056A1 (fr) 2012-11-02 2014-05-08 Pronova Biopharma Norge As Élimination de constituants indésirables à partir de compositions huileuses
AU2014358123B2 (en) 2013-12-04 2018-03-29 Nippon Suisan Kaisha, Ltd. Dihomo-gamma-linolenic acid-containing microbial oil and dihomo-gamma-linolenic acid-containing microbial biomass
CN120623044A (zh) 2014-09-17 2025-09-12 株式会社日水 含有二十碳五烯酸烷基酯的组合物及其制造方法
WO2017038860A1 (fr) 2015-08-31 2017-03-09 日本水産株式会社 Composition comprenant un acide gras polyinsaturé libre, et procédé de fabrication de celle-ci
ITUB20153877A1 (it) * 2015-09-24 2017-03-24 Tiberio Bruzzese Metodo di purificazione di gliceridi di acidi grassi, composizioni che ne derivano, e loro uso
CN106349070A (zh) * 2016-08-31 2017-01-25 山东康曼生物科技有限公司 一种从低含量乙酯鱼油生产欧米加‑3‑酸乙酯90的工艺
KR101988728B1 (ko) * 2016-09-23 2019-06-13 씨제이제일제당 (주) 지방산 에틸 에스테르의 제조방법
DK3649219T3 (en) * 2017-07-07 2022-10-24 Bunge Loders Croklaan B V Process for the preparation of a hydrogenated fat composition
CN109438220B (zh) * 2018-10-31 2021-04-13 苏州赛分科技有限公司 一种从鱼油中纯化epa的方法
KR20210108948A (ko) 2018-12-26 2021-09-03 닛신 파마 가부시키가이샤 에이코사펜타엔산 알킬에스테르 함유 조성물 및 그 제조 방법
CN111302940A (zh) * 2020-04-08 2020-06-19 燕园泽龙(涿鹿)生物科技有限公司 高纯度α-亚麻酸乙酯的生产方法
JP7289994B2 (ja) 2021-03-17 2023-06-12 株式会社ニッスイ 精製の方法および精製された製品
CN114057574A (zh) * 2021-12-03 2022-02-18 浙江工商大学 一种制备高纯度epa乙酯的方法

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0460917B1 (fr) 1990-06-04 1997-01-02 Nippon Suisan Kaisha, Ltd. Procédé de fabrication de l'acide eicosapentaénoique ou un de ses dérivés esters
JPH09510091A (ja) 1994-03-08 1997-10-14 ノルスク・ヒドロ・アクシェセルスカープ 精油組成物
JPH1095744A (ja) 1996-09-20 1998-04-14 Nof Corp 高度不飽和脂肪酸又はそのアルキルエステルの製造方法
JPH10310551A (ja) 1997-05-12 1998-11-24 Nippon Wax Polymer Kaihatsu Kenkyusho:Kk エイコサペンタエン酸又はそのエステルの精製方法
EP0610506B1 (fr) 1991-10-28 1999-06-23 Nippon Suisan Kabushiki Kaisha Procede de production d'acide eicosapentaenoique de haute purete ou d'un ester de celui-ci
JPH11209785A (ja) 1998-01-21 1999-08-03 Ikeda Shokken Kk 高純度高度不飽和脂肪酸の低級アルコールエステル精製方法
EP0712651B1 (fr) 1994-11-15 2000-02-02 K.D. Pharma Bexbach GmbH Procédé de récupération d'une substance ou d'un groupe de substances à partir d'un mélange
JP2001302584A (ja) 2000-02-17 2001-10-31 Sumitomo Chem Co Ltd 脂肪酸エステルの製造方法および脂肪酸エステルを含む燃料
WO2002006430A1 (fr) 2000-07-19 2002-01-24 Lysi Hf. Huiles marines presentant de faibles taux de contaminants
WO2004007654A1 (fr) 2002-07-11 2004-01-22 Pronova Biocare As Procede et fluide de travail volatile reduisant les polluants environnementaux presents dans des graisses ou des huiles, supplement dietetique, et produit alimentaire pour animaux
WO2011080503A2 (fr) 2009-12-30 2011-07-07 Equateq Limited Procédé de séparation chromatographique en lit mobile simulé
JP2011522913A (ja) 2008-05-15 2011-08-04 プロノヴァ バイオファーマ ノルゲ アーエス オキアミ油加工方法
EP2438819A1 (fr) 2009-06-02 2012-04-11 Golden Omega S.A. Procédé pour l'obtention d'un concentré d'esters d'acides eicosapentaénoïque et docosahexaénoïque
WO2012109539A1 (fr) 2011-02-11 2012-08-16 E. I. Du Pont De Nemours And Company Concentré d'acide eicosapentaénoïque
WO2013007315A1 (fr) 2011-07-14 2013-01-17 Soluciones Extractivas Alimentarias, S.L. Nouveau procédé de réduction des polluants dans les graisses et les huiles et leurs dérivés

Family Cites Families (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57149400A (en) 1981-03-12 1982-09-14 Kureha Chemical Ind Co Ltd Manufacture of high purity long chain highly unsaturated fatty acid ester
JPS5888339A (ja) 1981-11-20 1983-05-26 Kagakuhin Kensa Kyokai エイコサペンタエン酸又はそのエステルとドコサヘキサエン酸又はそのエステルの分離精製方法
NL8200559A (nl) 1982-02-15 1983-09-01 Ir Jan Bart Le Poole Prof Dr Bestralingsinrichting met bundelsplitsing.
JPS60208940A (ja) 1984-03-31 1985-10-21 Nippon Zeon Co Ltd 長鎮不飽和脂肪酸化合物の分離精製法
DE3524656A1 (de) * 1985-07-10 1987-01-15 Stage Hermann Verfahren und anlage zum desodorieren und/oder entsaeuern relativ kleiner, wechselnder chargen hochsiedender fluessigkeiten
JP2603830B2 (ja) * 1987-06-15 1997-04-23 日清製油株式会社 油脂の製造法
GB8819110D0 (en) 1988-08-11 1988-09-14 Norsk Hydro As Antihypertensive drug & method for production
JPH0633088B2 (ja) 1990-02-20 1994-05-02 金沢樹脂工業株式会社 組立式フォークリフト用パレット
JP3290152B2 (ja) 1990-06-04 2002-06-10 日本水産株式会社 高濃度エイコサペンタエン酸またはそのエステル
JPH07105223B2 (ja) 1991-03-11 1995-11-13 日本碍子株式会社 高温電池集合体
US5215630A (en) 1991-06-04 1993-06-01 Nippon Suisan Kaisha, Ltd. Method of purifying eicosapentaenoic acid or the ester derivative thereof by fractional distillation
JP2988754B2 (ja) 1991-09-03 1999-12-13 日本水産株式会社 高真空連続蒸留装置
JP3614177B2 (ja) 1992-07-21 2005-01-26 日本水産株式会社 高純度ドコサヘキサエン酸またはそのエステルの 製造方法
JPH08100191A (ja) * 1994-09-30 1996-04-16 Nisshin Flour Milling Co Ltd 高度不飽和脂肪酸またはそのエステルの精製方法
JPH09302380A (ja) * 1996-05-10 1997-11-25 Nippon Wax Polymer Kaihatsu Kenkyusho:Kk エイコサペンタエン酸又はそのエステルの精製方法
CN1072711C (zh) * 1998-01-05 2001-10-10 山东禹王制药有限公司 一种高度不饱和脂肪酸的工业化生产方法
PT1084214E (pt) 1998-06-05 2007-01-31 Merck Patent Gmbh Óleo marinho de teor reduzido de contaminantes
DE19923558A1 (de) 1999-05-21 2000-11-23 K D Pharma Bexbach Gmbh Verfahren zur Herstellung von geruchs- und geschmacksfreien ungesättigten Fettsäuren aus Naturölen und deren Verwendung
ES2159257B1 (es) 1999-11-19 2002-04-16 Kd Iqa S L Nuevo procedimiento de preparacion del ester etilico del acido eicosa pentaenoico.
EP1125914A1 (fr) 2000-02-14 2001-08-22 Nisshin Flour Milling Co., Ltd. Procédé de séparation et de purification d'acide eicosapentaénoique ou d'un ester de celui-ci
CA2336513C (fr) 2000-02-17 2010-08-24 Tatsuo Tateno Methode de production d'esters d'acide gras et combustibles contenant un ester d'acide gras
FR2894772B1 (fr) * 2005-12-20 2008-03-14 Pierre Fabre Medicament Sa Procede d'enrichissement en dha
DE102006012866B4 (de) 2006-03-19 2009-04-09 Uic Gmbh Verfahren zur Abtrennung leichtflüchtiger Komponenten aus einem Stoffgemisch sowie Vorrichtung zur Durchführung dieses Verfahrens
JP2008061571A (ja) 2006-09-07 2008-03-21 Toyomac Ltd 飼料用液状油脂の製造方法および配合飼料
WO2008133573A1 (fr) * 2007-04-26 2008-11-06 Patrick Adlercreutz Huile marine enrichie en acide gras polyinsaturé (pufa), comprenant l'acide eicosapentaénoïque (epa) et l'acide docosahexaénoïque (dha) et son procédé de fabrication
CN101765662B (zh) 2007-07-30 2014-04-02 日本水产株式会社 Epa浓缩油和dha浓缩油的制造方法
DK2062484T3 (da) 2007-11-23 2011-07-18 Reemtsma H F & Ph Fremgangsmåde til fremstilling af røgfri tobaksvarer og røgfri tobaksvare til oral konsumption
BRPI0909187A2 (pt) 2008-03-20 2015-08-04 Virun Inc Emulsões incluindo tocoferol de derivados de peg
KR101357298B1 (ko) 2008-06-20 2014-01-28 에이케이 앤 엠엔 바이오팜 주식회사 오메가-3계 고도불포화 지방산의 고순도 정제방법
JP2010118383A (ja) * 2008-11-11 2010-05-27 Nikon Corp 照明装置、露光装置、及びデバイス製造方法
MX2011009503A (es) 2009-03-09 2011-09-28 Pronova Biopharma Norge As Composiciones que comprenden una mezcla de aceite de acido graso y un tensioactivo, y metodos y usos de las mismas.
CN103037708B (zh) 2010-03-23 2015-05-20 维尔恩公司 含有蔗糖脂肪酸酯的纳米乳液
CN102959083B (zh) 2010-05-28 2016-01-20 日本水产株式会社 利用脂肪酶的含高度不饱和脂肪酸的油脂的制造方法
DK2580342T3 (da) * 2010-06-09 2019-07-01 Fermentalg Sammensætninger omfattende eicosapentaensyre egnet til høj oprensning
KR101904392B1 (ko) 2010-09-24 2018-10-05 프로노바 바이오파마 너지 에이에스 오메가-3 지방산을 농축하기 위한 공정
AU2011316139B2 (en) 2010-10-13 2016-07-07 Cognis Ip Management Gmbh Device and method for distilling temperature-sensitive substances
JP5650506B2 (ja) 2010-11-22 2015-01-07 優章 荒井 電解水の製造装置
GB201111591D0 (en) * 2011-07-06 2011-08-24 Equateq Ltd Further new process
EP2776544A1 (fr) * 2011-11-09 2014-09-17 Evonik Membrane Extraction Technology Limited Procédés membranaires pour la diminution d'au moins une impureté et fabrication d'un concentré comprenant au moins un composant naturel à partir d'un mélange huileux d'acides gras non marins, et compositions en résultant
US8258330B1 (en) 2012-01-04 2012-09-04 Naturalis, S.A. Carrier fluid composition comprising fatty acids ethyl esters and process for reducing the concentration of persistent organic pollutants in fish oil
KR102117806B1 (ko) * 2012-05-14 2020-06-01 닛폰 스이산 가부시키가이샤 환경 오염 물질을 저감시킨 고도 불포화 지방산 또는 고도 불포화 지방산 에틸에스테르 및 그 제조 방법
AU2014358123B2 (en) 2013-12-04 2018-03-29 Nippon Suisan Kaisha, Ltd. Dihomo-gamma-linolenic acid-containing microbial oil and dihomo-gamma-linolenic acid-containing microbial biomass

Patent Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0460917B1 (fr) 1990-06-04 1997-01-02 Nippon Suisan Kaisha, Ltd. Procédé de fabrication de l'acide eicosapentaénoique ou un de ses dérivés esters
EP0610506B1 (fr) 1991-10-28 1999-06-23 Nippon Suisan Kabushiki Kaisha Procede de production d'acide eicosapentaenoique de haute purete ou d'un ester de celui-ci
JPH09510091A (ja) 1994-03-08 1997-10-14 ノルスク・ヒドロ・アクシェセルスカープ 精油組成物
EP0712651B1 (fr) 1994-11-15 2000-02-02 K.D. Pharma Bexbach GmbH Procédé de récupération d'une substance ou d'un groupe de substances à partir d'un mélange
JPH1095744A (ja) 1996-09-20 1998-04-14 Nof Corp 高度不飽和脂肪酸又はそのアルキルエステルの製造方法
JPH10310551A (ja) 1997-05-12 1998-11-24 Nippon Wax Polymer Kaihatsu Kenkyusho:Kk エイコサペンタエン酸又はそのエステルの精製方法
JPH11209785A (ja) 1998-01-21 1999-08-03 Ikeda Shokken Kk 高純度高度不飽和脂肪酸の低級アルコールエステル精製方法
JP2001302584A (ja) 2000-02-17 2001-10-31 Sumitomo Chem Co Ltd 脂肪酸エステルの製造方法および脂肪酸エステルを含む燃料
WO2002006430A1 (fr) 2000-07-19 2002-01-24 Lysi Hf. Huiles marines presentant de faibles taux de contaminants
WO2004007654A1 (fr) 2002-07-11 2004-01-22 Pronova Biocare As Procede et fluide de travail volatile reduisant les polluants environnementaux presents dans des graisses ou des huiles, supplement dietetique, et produit alimentaire pour animaux
EP1523541B1 (fr) 2002-07-11 2009-12-30 Pronova BioPharma Norge AS Procédé et fluide volatile reduisant les polluants environnementaux présents dans des graisses ou des huiles, supplément dietetique, et produit alimentaire pour animaux
JP2011522913A (ja) 2008-05-15 2011-08-04 プロノヴァ バイオファーマ ノルゲ アーエス オキアミ油加工方法
EP2438819A1 (fr) 2009-06-02 2012-04-11 Golden Omega S.A. Procédé pour l'obtention d'un concentré d'esters d'acides eicosapentaénoïque et docosahexaénoïque
WO2011080503A2 (fr) 2009-12-30 2011-07-07 Equateq Limited Procédé de séparation chromatographique en lit mobile simulé
WO2012109539A1 (fr) 2011-02-11 2012-08-16 E. I. Du Pont De Nemours And Company Concentré d'acide eicosapentaénoïque
WO2013007315A1 (fr) 2011-07-14 2013-01-17 Soluciones Extractivas Alimentarias, S.L. Nouveau procédé de réduction des polluants dans les graisses et les huiles et leurs dérivés
EP2732014B1 (fr) 2011-07-14 2018-03-14 Soluciones Extractivas Alimentarias, S.L. Nouveau procédé de réduction des polluants dans les graisses et les huiles et leurs dérivés

Non-Patent Citations (18)

* Cited by examiner, † Cited by third party
Title
"Chemical Engineering and Chemical Process Technology: v.2.", vol. 2, 30 November 2010, EOLSS PUBLICATIONS, ISBN: 978-1-84826-847-0, article STICHLMAIR, J.G.: "Distillation or Rectification", pages: 68 - 92, XP009552603
"Encyclopaedia Chimica 5", 1 January 1961, KYORITSI SHURPAN, Japan, article EDITED BY CHEMISTRY DICTIONARY EDITORIAL COMMITTEE: "DEFINITION OF RECTIFICATION", pages: 282 - 283, XP009554235
"Encyclopaedia Chimica 6", 1 January 1961, KYORITSI SHUPPAN, Japan, article EDITED BY CHEMISTRY DICTIONARY EDITORIAL COMMITTEE: "DEFINITION OF UREA ADDUCT PROCESS", pages: 826 - 829, XP009554234
"Introduction to Supercritical Fluids", 31 December 2020, Japan, ISBN: 978-4-621-08061-0, article EDITOR-IN-CHIEF, SUPERCRITICAL FLUID SECTION, SOCIETY OF CHEMICAL ENGINEERING: "4.1 Principle of supercritical fluid extraction separation", pages: 67 - 69, XP009554223
"Persistent Organic Pollutants", 1 January 2019, INTECHOPEN, article ZACHARIA JAMES T.: "Chapter 3 - Degradation Pathways of Persistent Organic Pollutants (POPs) in the Environment (passage)", pages: 17 - 20, XP093130910, DOI: 10.5772/intechopen.79645
BIMBO, ANTHONY P.: "Guidelines for characterising food grade fish oil", INFORM, vol. 9, no. 5, 1998, pages 473 - 483, XP008078334
BREIVIK HARALD: "Long-chain omega-3 specialty oils", 1 January 2007, WOODHEAD PUBLISHING LTD., pages: 92 - 95, XP093130918
BREIVIK, HARALD ET AL.: "Removal of organic environmental pollutants from fish oil by short-path distillation", LIPID TECHNOLOGY, vol. 17, no. 3, 2005, pages 55 - 58, XP009177680
CMOLIK J, POKORNY J: "PHYSICAL REFINING OF EDIBLE OILS", EUROPEAN JOURNAL OF LIPID SCIENCE TECHNOLOGY, vol. 102, no. 7, 1 July 2000 (2000-07-01), DE , pages 472 - 486, XP000958233, ISSN: 1438-7697
COURTNEY, E. D. ET AL.: "Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas", INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, vol. 22, no. 7, 2007, pages 765 - 776, XP037838127, DOI: 10.1007/s00384-006-0240-4
FOURNIER VÉRONIQUE, DESTAILLATS FRÉDÉRIC, JUANÉDA PIERRE, DIONISI FABIOLA, LAMBELET PIERRE, SÉBÉDIO JEAN‐LOUIS, BERDEAUX OLIVIER: "Thermal degradation of long‐chain polyunsaturated fatty acids during deodorization of fish oil", EUROPEAN JOURNAL OF LIPID SCIENCE TECHNOLOGY, vol. 108, no. 1, 1 January 2006 (2006-01-01), DE , pages 33 - 42, XP055963966, ISSN: 1438-7697, DOI: 10.1002/ejlt.200500290
JULSHAMN, K. ET AL.: "Removal of DDT and its metabolites from fish oils by molecular distillation", FISKERIDIREKTORATETS SKRIFTER SERIE TEKNOLOGISKE UNDERSMKELSER, vol. 5, no. 15, 1973, pages 3 - 11, XP002971951
OTERHALS AGE: "Methods for removal of pollutants in fishmeal and fish oil ", LECTURE MARING FAG DAY, 31 May 2005 (2005-05-31), XP093130930
ROBERT S. LEES AND MARCUS KAREL: "Omega-3 Fatty Acids in Health and Disease", 1 January 1990, MARCEL DEKKER, INC., article ACKMAN ROBERT G., W.M.N. RATNAYAKE: "Chapter 10 (passage)", pages: 215, 219, XP093130923
RYUJI YAMAMURA ET AL.: "High Purification of Polyunsaturated Fatty Acids", JOURNAL OF JAPAN OIL CHEMISTS' SOCIETY, vol. 47, no. 5, 1998, pages 449 - 456, XP008175194
VOGEL, A. I.; FURNISS, B.S.; HANNAFORD, A.J.; SMITH, P.W.G.; TATCHELL, A.R.: "Vogel's Textbook of Practical Organic Chemistry", 1 January 1989, ADDISON WESLEY LONGMAN LIMITED , ISBN: 0-582-46236-3, article BRIAN S FURNISS; ANTONY J HANNAFORD; PETER W G SMITH; AUSTIN R TATCHELL: "2.28 High vacuum distillation - molecular distillation", pages: 186 - 191, XP009553481
WEST NICHOLAS J, CLARK SUSAN K, PHILLIPS ROBIN K S: "Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis", GUT, vol. 59, no. 7, 1 July 2010 (2010-07-01), pages 918 - 925, XP055963949, DOI: 10.1136/gut.2009.200642
YUSHI, vol. 62, no. 11, 2009, pages 38 - 39

Also Published As

Publication number Publication date
CN104302615A (zh) 2015-01-21
US20180305291A1 (en) 2018-10-25
JP2024069262A (ja) 2024-05-21
KR102229106B1 (ko) 2021-03-18
US10399923B2 (en) 2019-09-03
JP2022132317A (ja) 2022-09-08
KR20250164338A (ko) 2025-11-24
CA2873160C (fr) 2024-02-27
JP2019031507A (ja) 2019-02-28
KR20210030507A (ko) 2021-03-17
JP2017190335A (ja) 2017-10-19
KR20220140655A (ko) 2022-10-18
EP2851361A1 (fr) 2015-03-25
EP3971165A1 (fr) 2022-03-23
CN113025434A (zh) 2021-06-25
US20210269388A1 (en) 2021-09-02
DE202013012875U1 (de) 2021-01-15
US20230183165A1 (en) 2023-06-15
KR102453616B1 (ko) 2022-10-11
JP2021004254A (ja) 2021-01-14
KR20200023557A (ko) 2020-03-04
PE20241184A1 (es) 2024-06-03
CN107602378B (zh) 2021-06-25
CN106810446A (zh) 2017-06-09
KR102117725B1 (ko) 2020-06-01
KR20240096704A (ko) 2024-06-26
EP4414356A3 (fr) 2024-12-25
PE20190969A1 (es) 2019-07-08
US20150126760A1 (en) 2015-05-07
JPWO2013172346A1 (ja) 2016-01-12
ES2985397T3 (es) 2024-11-05
US20250243146A1 (en) 2025-07-31
JP6434573B2 (ja) 2018-12-05
EP3971165B1 (fr) 2024-08-07
JP2018111719A (ja) 2018-07-19
CN113025434B (zh) 2025-05-02
CN107602378A (zh) 2018-01-19
CA3225865A1 (fr) 2013-11-21
CL2014003053A1 (es) 2015-02-27
US10399922B2 (en) 2019-09-03
CN104302615B (zh) 2017-09-08
EP4414356A2 (fr) 2024-08-14
US11603347B2 (en) 2023-03-14
JP6389579B2 (ja) 2018-09-12
JP5592570B2 (ja) 2014-09-17
JP2014231513A (ja) 2014-12-11
US11034643B2 (en) 2021-06-15
JP6774469B2 (ja) 2020-10-21
HUE057283T2 (hu) 2022-04-28
DK2851361T3 (da) 2022-01-03
CN113045422A (zh) 2021-06-29
KR20220044387A (ko) 2022-04-07
EP3971165C0 (fr) 2024-08-07
ES2900618T3 (es) 2022-03-17
KR20200060531A (ko) 2020-05-29
EP2851361A4 (fr) 2015-12-30
US12331015B2 (en) 2025-06-17
CA2873160A1 (fr) 2013-11-21
WO2013172346A1 (fr) 2013-11-21
US20190337883A1 (en) 2019-11-07
KR102117806B1 (ko) 2020-06-01
KR20150013257A (ko) 2015-02-04
KR102381331B1 (ko) 2022-04-01
US9540306B2 (en) 2017-01-10
US20170081272A1 (en) 2017-03-23
JP6309828B2 (ja) 2018-04-11
PE20142380A1 (es) 2015-01-21

Similar Documents

Publication Publication Date Title
US12331015B2 (en) Highly unsaturated fatty acid or highly unsaturated fatty acid ethyl ester with reduced environmental pollutants, and method for producing same
HK40057853A (en) Highly unsaturated fatty acid or highly unsaturated fatty acid ethyl ester, pharmaceutical, additive or food

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20141205

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAX Request for extension of the european patent (deleted)
RA4 Supplementary search report drawn up and despatched (corrected)

Effective date: 20151130

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

R17P Request for examination filed (corrected)

Effective date: 20141205

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20171005

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

RIC1 Information provided on ipc code assigned before grant

Ipc: C07C 69/587 20060101AFI20210507BHEP

Ipc: A61K 31/20 20060101ALI20210507BHEP

Ipc: A61K 31/202 20060101ALI20210507BHEP

Ipc: A61K 31/232 20060101ALI20210507BHEP

Ipc: A61K 35/12 20150101ALI20210507BHEP

Ipc: A61K 35/56 20150101ALI20210507BHEP

Ipc: A61K 35/60 20060101ALI20210507BHEP

Ipc: A61K 35/66 20150101ALI20210507BHEP

Ipc: A61P 3/02 20060101ALI20210507BHEP

Ipc: C07C 67/54 20060101ALI20210507BHEP

Ipc: C07C 67/56 20060101ALI20210507BHEP

INTG Intention to grant announced

Effective date: 20210611

RIN1 Information on inventor provided before grant (corrected)

Inventor name: DOISAKI, NOBUSHIGE

Inventor name: HATA, KAZUHIKO

Inventor name: TOKIWA, SHINJI

Inventor name: MATSUSHIMA, KAZUNORI

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 1449756

Country of ref document: AT

Kind code of ref document: T

Effective date: 20211215

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602013080190

Country of ref document: DE

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

Effective date: 20211220

REG Reference to a national code

Ref country code: NL

Ref legal event code: FP

REG Reference to a national code

Ref country code: NO

Ref legal event code: T2

Effective date: 20211124

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2900618

Country of ref document: ES

Kind code of ref document: T3

Effective date: 20220317

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG9D

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 1449756

Country of ref document: AT

Kind code of ref document: T

Effective date: 20211124

REG Reference to a national code

Ref country code: HU

Ref legal event code: AG4A

Ref document number: E057283

Country of ref document: HU

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20220224

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20220324

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20220324

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20220225

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

REG Reference to a national code

Ref country code: DE

Ref legal event code: R026

Ref document number: 602013080190

Country of ref document: DE

PLBI Opposition filed

Free format text: ORIGINAL CODE: 0009260

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

PLAX Notice of opposition and request to file observation + time limit sent

Free format text: ORIGINAL CODE: EPIDOSNOBS2

26 Opposition filed

Opponent name: K.D. PHARMA BEXBACH GMBH

Effective date: 20220824

R26 Opposition filed (corrected)

Opponent name: K.D. PHARMA BEXBACH GMBH

Effective date: 20220824

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

PLBB Reply of patent proprietor to notice(s) of opposition received

Free format text: ORIGINAL CODE: EPIDOSNOBS3

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20220514

RAP4 Party data changed (patent owner data changed or rights of a patent transferred)

Owner name: NISSUI CORPORATION

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 11

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20220514

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20231117

APAH Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOSCREFNO

APBM Appeal reference recorded

Free format text: ORIGINAL CODE: EPIDOSNREFNO

APBP Date of receipt of notice of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA2O

APBQ Date of receipt of statement of grounds of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA3O

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20211124

APAH Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOSCREFNO

REG Reference to a national code

Ref country code: DE

Ref legal event code: R081

Ref document number: 602013080190

Country of ref document: DE

Owner name: NISSUI CORPORATION, JP

Free format text: FORMER OWNER: NIPPON SUISAN KAISHA, LTD., MINATO-KU, TOKYO, JP

REG Reference to a national code

Ref country code: HU

Ref legal event code: HC9C

Owner name: NISSUI CORPORATION, JP

Free format text: FORMER OWNER(S): NIPPON SUISAN KAISHA, LTD., JP

REG Reference to a national code

Ref country code: NL

Ref legal event code: PD

Owner name: NISSUI CORPORATION; JP

Free format text: DETAILS ASSIGNMENT: CHANGE OF OWNER(S), CHANGE OF LEGAL ENTITY; FORMER OWNER NAME: NIPPON SUISAN KAISHA, LTD.

Effective date: 20241204

REG Reference to a national code

Ref country code: BE

Ref legal event code: HC

Owner name: NISSUI CORPORATION; JP

Free format text: DETAILS ASSIGNMENT: CHANGE OF OWNER(S), CHANGE OF OWNER(S) NAME; FORMER OWNER NAME: NIPPON SUISAN KAISHA, LTD.

Effective date: 20241113

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20250317

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20250409

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20250402

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 20250602

Year of fee payment: 13

Ref country code: DK

Payment date: 20250516

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: HU

Payment date: 20250429

Year of fee payment: 13

Ref country code: NO

Payment date: 20250509

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 20250410

Year of fee payment: 13

Ref country code: IT

Payment date: 20250422

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20250401

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 20250601

Year of fee payment: 13